The primary objective of this program is to determine the efficacy of hyperthermia as a therapeutic modality, used either alone or in combination with radiation or chemotherapy, in the treatment of human malignancies. This program also will continue to study the mechanisms by which heat affects biological systems and the physical principles of producing and measuring thermal distributions in animals and humans. The proposed research involved a multidisciplinary effort, including biological, physical and clinical scientists. Specific projects within this program will study a broad range of the biological effects of hyperthermia with the goal to further establish the rationale for its use in cancer therapy. The biological studies span molecular and biochemical, cellular and organized tissue systems, and include investigations using both animal and human cells and tissues. The physics and engineering projects will focus their studies on developing techniques to produce elevated temperature distributions in biological systems and, then to measure the resulting temperature, and other field, patterns. Hyperthermic fields will be produced using radiofrequency (rf), including invasive resistive, external capacitive and magnetic inductive, and microwave techniques. The clinical projects are designed to ascertain the efficacy of either localized or regional hyperthermia combined with radiation or chemotherapeutic drugs. While a variety of tumor types will be treated with these combinations, specific Phase II clinical trials will be conducted, including the use of interstitial thermoradiotherapy in the treatment of stage 3B cervical cancers, rf and microwave induced hyperthermia combined with radiation in the treatment of malignant melanoma, and Phase I/II studies on the combination of regional hyperthermia, using magnetic induction techniques, combined with radiation in the treatment of squamous cell carcinoma of the lung. A Phase I studY of the combination of local or regional hyperthermia with specific chemotherapeutic drugs will also be conducted. Thus, this program is designed to investigate, in a comprehensive manner, the basic biological and physical principles of hyperthermia, and then, to determine the usefulness of this modality in combination with radiation and drugs in cancer therapy.